JP4094679B2 - C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 - Google Patents
C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 Download PDFInfo
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/811,566 US6127116A (en) | 1995-08-29 | 1997-03-04 | Functional DNA clone for hepatitis C virus (HCV) and uses thereof |
| US08/811,566 | 1997-03-04 | ||
| PCT/US1998/004428 WO1998039031A1 (en) | 1997-03-04 | 1998-02-26 | Functional dna clone for hepatitis c virus (hcv) and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007339488A Division JP4223068B2 (ja) | 1997-03-04 | 2007-12-28 | C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001515353A JP2001515353A (ja) | 2001-09-18 |
| JP2001515353A5 JP2001515353A5 (https=) | 2007-05-10 |
| JP4094679B2 true JP4094679B2 (ja) | 2008-06-04 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP53885498A Expired - Lifetime JP4094679B2 (ja) | 1997-03-04 | 1998-02-26 | C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 |
| JP2007339488A Expired - Lifetime JP4223068B2 (ja) | 1997-03-04 | 2007-12-28 | C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007339488A Expired - Lifetime JP4223068B2 (ja) | 1997-03-04 | 2007-12-28 | C型肝炎ウイルス(hcv)用の機能性dnaクローン及びその使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (4) | US6127116A (https=) |
| EP (1) | EP1005366A4 (https=) |
| JP (2) | JP4094679B2 (https=) |
| AU (1) | AU742175B2 (https=) |
| BR (1) | BR9808147A (https=) |
| CA (1) | CA2283464C (https=) |
| IL (2) | IL131688A0 (https=) |
| WO (1) | WO1998039031A1 (https=) |
| ZA (1) | ZA981838B (https=) |
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| US6153421A (en) * | 1997-07-18 | 2000-11-28 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Cloned genomes of infectious hepatitis C viruses and uses thereof |
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| US20030028011A1 (en) * | 1997-07-30 | 2003-02-06 | Parkin Neil T. | Compositions and methods for determining susceptibility of hepatitis C virus to anti-viral drugs |
| US6893866B1 (en) * | 1997-11-28 | 2005-05-17 | The Crown In The Right Of The Queensland Department Of Health | Flavivirus expression and delivery system |
| DE19915178A1 (de) * | 1999-04-03 | 2000-10-05 | Univ Mainz Johannes Gutenberg | Hepatitis C Virus Zellkultursystem |
| US6479504B1 (en) | 1999-06-16 | 2002-11-12 | The University Of Iowa Research Foundation | Antagonism of immunostimulatory CpG-oligonucleotides by 4-aminoquinolines and other weak bases |
| ATE395930T1 (de) * | 1999-10-22 | 2008-06-15 | Aventis Pasteur | Verfahren zur erregung und/oder verstärkung der immunantwort gegen tumorantigene |
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| US6921634B2 (en) * | 1999-12-23 | 2005-07-26 | Board Of Regents, The University Of Texas System | Replication competent hepatitus C virus and methods of use |
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| EP1381673B1 (en) * | 2001-03-27 | 2009-05-13 | Vertex Pharmaceuticals Incorporated | Compositions and methods useful for hcv infection |
| FR2824072B1 (fr) * | 2001-04-27 | 2004-03-12 | Centre Nat Rech Scient | Procede de replication et de production du virus de l'hepatite c |
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| WO2002089840A1 (en) * | 2001-05-10 | 2002-11-14 | The Regents Of The University Of California | Recombinant bicistronic flaviviruses and methods of use thereof |
| US20050209180A1 (en) * | 2001-05-18 | 2005-09-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA) |
| US20060211642A1 (en) * | 2001-05-18 | 2006-09-21 | Sirna Therapeutics, Inc. | RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA) |
| US20040209831A1 (en) * | 2002-02-20 | 2004-10-21 | Mcswiggen James | RNA interference mediated inhibition of hepatitis C virus (HCV) gene expression using short interfering nucleic acid (siNA) |
| WO2003040356A1 (en) * | 2001-08-06 | 2003-05-15 | Yangling Daiying Biological Engineering Co., Ltd | The intact hepatitis c virus and the method for culturing it in a vitro cell culture |
| CA2461380C (en) * | 2001-10-11 | 2011-03-22 | Merck & Co., Inc. | Hepatitis c virus vaccine |
| US6689559B2 (en) * | 2001-11-29 | 2004-02-10 | The Research Foundation Of The State University Of New York | Efficient hepatitis C virus replicon and its use in identifying antiviral compounds |
| ES2346717T3 (es) * | 2002-03-11 | 2010-10-19 | Lab 21 Limited | Metodo y composiciones para identificar y caracterizar la hepatitis c. |
| KR100471946B1 (ko) * | 2002-05-08 | 2005-03-08 | (주)팬바이오넷 | C형 간염바이러스(hcv)의 리플리콘, 이를 포함하는세포주, 및 상기 세포주를 이용한 hcv 탐지방법 |
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| GB0222824D0 (en) * | 2002-10-02 | 2002-11-06 | Moredun Res Inst | Bacteriophage-mediated immunisation II |
| CA2868618C (en) * | 2002-10-16 | 2017-05-23 | Gen-Probe Incorporated | Compositions and methods for detecting west nile virus |
| US7927840B2 (en) | 2006-09-11 | 2011-04-19 | Gen Probe Incorporated | Method for detecting West Nile Virus nucleic acids in the 3′ non-coding region |
| WO2004037284A1 (en) * | 2002-10-22 | 2004-05-06 | Sanofi Pasteur Limited | Anti-cancer vaccines and high-dose cytokines as adjuvants |
| JP2006506074A (ja) * | 2002-11-13 | 2006-02-23 | ワシントン ユニヴァーシティー | C型肝炎ウイルスの複製に対して高許容性である細胞系 |
| WO2005054450A1 (en) * | 2003-12-01 | 2005-06-16 | Vertex Pharmaceuticals Incorporated | Compositions comprising fetal liver cells and methods useful for hcv infection |
| EP2423216B1 (en) | 2003-12-01 | 2015-07-08 | Board Of Regents, The University Of Texas System | Replication competent hepatitis C virus and methods of use |
| ATE491810T1 (de) * | 2004-01-23 | 2011-01-15 | Bio Merieux Inc | Neuartiges nukleotidgemisch für eine verbesserte nukleinsäurenamplifikationsleistung |
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| AU2005222084B2 (en) | 2004-03-05 | 2010-04-22 | Benitec, Inc. | Multiple promoter expression cassettes for simultaneous delivery of RNAI agents |
| US7833987B2 (en) * | 2004-03-12 | 2010-11-16 | Indian Institute Of Science | Small synthetic RNA, a method of preparing the same and uses thereof |
| EP1792181B1 (en) * | 2004-06-21 | 2010-11-17 | Progenra Inc. | Diagnostic and screening methods and kits associated with proteolytic activity |
| US7785875B2 (en) | 2004-07-03 | 2010-08-31 | Mogam Biotechnology Research Institute | Polynucleotide encoding HCV epitopes which can bind to various HLA supertypes, immunogenic composition comprising same and method of inducing an HCV-specific immune response using same |
| ATE474587T1 (de) * | 2004-09-29 | 2010-08-15 | Univ Tulane | Inhibitoren des hepatitis-c-virus |
| CA2597655A1 (en) * | 2005-02-16 | 2006-08-24 | The Council Of The Queensland Institute Of Medical Research | Flavivirus replicon constructs for tumour therapy |
| AU2006220887B2 (en) * | 2005-03-04 | 2010-11-04 | The Rockefeller University | Infectious, chimeric Hepatitis C Virus, methods of producing the same and methods of use thereof |
| US20060234348A1 (en) * | 2005-04-13 | 2006-10-19 | Bujarski Jozef J | Method of production of RNA polymerase protein |
| JP2007312649A (ja) * | 2006-05-24 | 2007-12-06 | Japan Health Science Foundation | 再構築された感染性レトロウイルスゲノムクローンdna及びそれを含む微生物ならびにそれらの製造方法 |
| AU2015234338C1 (en) * | 2006-07-28 | 2017-07-20 | The Trustees Of The University Of Pennsylvania | Improved vaccines and methods for using the same |
| US7504255B2 (en) * | 2006-08-17 | 2009-03-17 | Saint Louis University | Compositions and methods for generation of infectious hepatitis C virus in immortalized human hepatocytes |
| US20080096274A1 (en) * | 2006-10-24 | 2008-04-24 | Guangpu Li | Recombinant alphavirus vectors and methods of using same |
| JP5627464B2 (ja) * | 2007-11-26 | 2014-11-19 | ノバルティス アーゲー | アルファウイルス粒子を生成する方法 |
| US8921536B2 (en) | 2008-10-29 | 2014-12-30 | The Trustees Of The University Of Pennsylvania | HCV vaccines and methods for using the same |
| US8829174B2 (en) | 2008-10-29 | 2014-09-09 | The Trustees Of The University Of Pennsylvania | HCV vaccines and methods for using the same |
| US20100129902A1 (en) | 2008-11-24 | 2010-05-27 | Erhard Ralf Schoenbrunner | Replication Stable and RNase Resistant Chimeras of Pestivirus with Insertion in 3' Nontranslated Region (3'NTR) |
| US8609403B2 (en) * | 2009-08-28 | 2013-12-17 | Tokyo Metropolitan Institute Of Medical Science | Polynucleotide derived from novel hepatitis C virus strain and use thereof |
| US20110070199A1 (en) * | 2009-09-21 | 2011-03-24 | Scheiber Ii Lane Bernard | Adaptable modified virus vector to deliver ribosomal ribonucleic acid combined with messenger ribonucleic acid as a medical treatment device to manage diabetes mellitus and other protein deficient dieases |
| CN103649316B (zh) | 2011-05-02 | 2017-07-28 | 约翰霍普金斯大学 | 合成的丙型肝炎基因组和制备及使用方法 |
| EP2744894A4 (en) * | 2011-08-18 | 2015-04-22 | Ycine Llc | PRODUCTION OF INFECTIOUS RNA VIRUSES IN YEAST |
| CA2962696A1 (en) | 2014-10-01 | 2016-04-07 | National Research Council Of Canada | Animal models, cell lines and methods for screening hepatitis c virus vaccines |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4631211A (en) * | 1985-03-25 | 1986-12-23 | Scripps Clinic & Research Foundation | Means for sequential solid phase organic synthesis and methods using the same |
| US5218099A (en) * | 1986-04-01 | 1993-06-08 | The United States Of America As Represented By The Department Of Health And Human Services | Post-transfusion, non-A, non-B hepatitis virus polynucleotides |
| ES2061500T5 (es) * | 1986-06-17 | 2003-05-16 | Chiron Corp | Diagnosis y vacunas de la hepatitis delta, su preparacion y uso. |
| US5656731A (en) * | 1987-10-15 | 1997-08-12 | Chiron Corporation | Nucleic acid-amplified immunoassay probes |
| US5714596A (en) * | 1987-11-18 | 1998-02-03 | Chiron Corporation | NANBV diagnostics: polynucleotides useful for screening for hepatitis C virus |
| US5712088A (en) * | 1987-11-18 | 1998-01-27 | Chiron Corporation | Methods for detecting Hepatitis C virus using polynucleotides specific for same |
| US5683864A (en) * | 1987-11-18 | 1997-11-04 | Chiron Corporation | Combinations of hepatitis C virus (HCV) antigens for use in immunoassays for anti-HCV antibodies |
| NZ227011A (en) * | 1987-11-18 | 1992-03-26 | Chiron Corp | Non-a, non-b-hepatitis (hepatitis c) antigens, proteins, nucleotide sequences, vaccines and kits |
| US5679342A (en) * | 1987-11-18 | 1997-10-21 | Chiron Corporation | Hepatitis C virus infected cell systems |
| US5698390A (en) * | 1987-11-18 | 1997-12-16 | Chiron Corporation | Hepatitis C immunoassays |
| GB2212511B (en) * | 1987-11-18 | 1992-01-22 | Chiron Corp | Hepatitis c virus |
| US5350671A (en) * | 1987-11-18 | 1994-09-27 | Chiron Corporation | HCV immunoassays employing C domain antigens |
| US5312737A (en) * | 1988-03-11 | 1994-05-17 | Abbott Laboratories | CKS method of HCV protein synthesis |
| US5010175A (en) * | 1988-05-02 | 1991-04-23 | The Regents Of The University Of California | General method for producing and selecting peptides with specific properties |
| US5191064A (en) * | 1988-09-30 | 1993-03-02 | The Research Foundation For Microbial Diseases (Osaka University) | Non-a, non-b hepatitis virus antigen peptide |
| JPH02167081A (ja) * | 1988-12-21 | 1990-06-27 | Tetsuo Nakamura | 非A非B型肝炎ウイルスゲノムRNA、cDNAおよびウイルス抗原蛋白質 |
| US5176994A (en) * | 1988-12-21 | 1993-01-05 | Immuno Japan Inc. | Non-A, Non-B hepatitis virus genome RNA, cDNA and virus antigen protein |
| US5354844A (en) * | 1989-03-16 | 1994-10-11 | Boehringer Ingelheim International Gmbh | Protein-polycation conjugates |
| KR0185373B1 (ko) * | 1989-03-17 | 1999-05-01 | 로버트 피. 블랙버언 | Hcv 폴리단백질에서 유래되는 hcv 아미노산 서열 부분을 포함하는 폴리펩티드 및 그 사용 |
| EP0414475B1 (en) * | 1989-08-25 | 1997-12-10 | Chiron Corporation | Methods for culturing HCV in B- or T-lymphocyte cell lines |
| US5372928A (en) * | 1989-09-15 | 1994-12-13 | Chiron Corporation | Hepatitis C virus isolates |
| KR940000755B1 (ko) * | 1990-02-16 | 1994-01-29 | 유나이티드 바이오메디칼 인코오포레이티드 | Hcv에 대한 항체 검출, hcv 감염의 진단 및 백신으로서의 그 예방에 특히 적합한 합성 펩티드 |
| US5106726A (en) * | 1990-02-16 | 1992-04-21 | United Biomedical, Inc. | Synthetic peptides specific for the detection of antibodies to HCV |
| ATE270326T1 (de) * | 1990-04-04 | 2004-07-15 | Chiron Corp | Protease von hepatitis-c-virus |
| HU217025B (hu) * | 1990-04-04 | 1999-11-29 | Chiron Corp. | Hepatitis C vírus-(HCV) antigénkészítmények az anti-HCV-antitestek kimutatására immunoassay-kben |
| CA2079912C (en) * | 1990-04-06 | 2000-07-11 | Gregory Reyes | Hepatitis c virus epitopes |
| WO1992000328A1 (en) * | 1990-06-30 | 1992-01-09 | Akzo N.V. | Non-a non-b sequences |
| KR0181517B1 (ko) * | 1990-07-09 | 1999-04-01 | 나까하라 노부유끼 | 비-에이 비-비형 간염-특이 항원 및 간염 진단에서 그의 용도 |
| EP0842947B2 (en) * | 1990-11-08 | 2009-03-18 | Novartis Vaccines and Diagnostics, Inc. | Hepatitis C virus asialoglycoproteins |
| US5654179A (en) * | 1990-11-14 | 1997-08-05 | Hri Research, Inc. | Nucleic acid preparation methods |
| EP0510952A1 (en) * | 1991-04-26 | 1992-10-28 | Immuno Japan Inc. | Oligonucleotide primers and their application for high-fidelity detection of non-a, non-b hepatitis virus |
| JPH06508024A (ja) * | 1991-06-10 | 1994-09-14 | ラッキー・リミテッド | C型肝炎診断試薬およびワクチン |
| WO1993000365A2 (en) * | 1991-06-24 | 1993-01-07 | Chiron Corporation | Hepatitis c virus (hcv) polypeptides |
| CA2116543C (en) * | 1991-07-31 | 2007-10-02 | Kay S. Greisen | Methods and reagents for detection of bacteria in cerebrospinal fluid |
| US5428145A (en) * | 1991-08-09 | 1995-06-27 | Immuno Japan, Inc. | Non-A, non-B, hepatitis virus genome, polynucleotides, polypeptides, antigen, antibody and detection systems |
| ATE161291T1 (de) * | 1991-08-27 | 1998-01-15 | Hoffmann La Roche | Verfahren und reagenzien zum nachweis von hepatitis c |
| US5427909A (en) * | 1991-09-09 | 1995-06-27 | Immuno Japan Inc. | Oligonucleotides and determination system of HCV genotypes |
| WO1993006126A1 (en) * | 1991-09-13 | 1993-04-01 | Chiron Corporation | Immunoreactive hepatitis c virus polypeptide compositions |
| US5576302A (en) * | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
| EP0627000B1 (en) * | 1992-01-31 | 2003-10-29 | Abbott Laboratories | Mammalian expression systems for hcv proteins |
| JPH06105690A (ja) * | 1992-03-10 | 1994-04-19 | Kunitada Shimotoono | 血液伝播性非a非b型肝炎ウィルスdna |
| US5643578A (en) * | 1992-03-23 | 1997-07-01 | University Of Massachusetts Medical Center | Immunization by inoculation of DNA transcription unit |
| US5610054A (en) * | 1992-05-14 | 1997-03-11 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecule targeted against Hepatitis C virus |
| US5552310A (en) * | 1992-06-12 | 1996-09-03 | Hiroshi Yoshikura | Replication of hepatitis C virus genome and identification of virus having high infectivity |
| JP2778886B2 (ja) * | 1992-10-16 | 1998-07-23 | エバーニュー バイオテック インコーポレイティド | C型肝炎ウィルスのコア抗原タンパク質及びそれを用いての診断方法及びキット |
| JPH06153961A (ja) * | 1992-11-27 | 1994-06-03 | Imuno Japan:Kk | C型肝炎ウイルス部分遺伝子、ならびにc型肝炎ウイルス遺 伝子の高感度検出法 |
| AU6364094A (en) * | 1993-03-12 | 1994-09-26 | Board Of Regents, The University Of Texas System | Anthracyclines with unusually high activity against cells resistant to doxorubicin and its analogs |
| TW275068B (https=) * | 1993-09-24 | 1996-05-01 | American Cyanamid Co | |
| ATE475668T1 (de) * | 1994-01-27 | 2010-08-15 | Univ Massachusetts Medical | Immunisierung durch impfung von dns transkriptionseinheit |
| US5861267A (en) * | 1995-05-01 | 1999-01-19 | Vertex Pharmaceuticals Incorporated | Methods, nucleotide sequences and host cells for assaying exogenous and endogenous protease activity |
| US5874565A (en) * | 1995-08-29 | 1999-02-23 | Washington University | Nucleic acids comprising a highly conserved novel 3 terminal sequence element of the hepatitis C virus |
| US5677124A (en) * | 1996-07-03 | 1997-10-14 | Ambion, Inc. | Ribonuclease resistant viral RNA standards |
| US6153421A (en) * | 1997-07-18 | 2000-11-28 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Cloned genomes of infectious hepatitis C viruses and uses thereof |
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- 1997-03-04 US US08/811,566 patent/US6127116A/en not_active Expired - Lifetime
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| BR9808147A (pt) | 2000-03-28 |
| US6127116A (en) | 2000-10-03 |
| CA2283464C (en) | 2006-09-26 |
| AU742175B2 (en) | 2001-12-20 |
| WO1998039031A1 (en) | 1998-09-11 |
| ZA981838B (en) | 1999-02-19 |
| JP2001515353A (ja) | 2001-09-18 |
| EP1005366A1 (en) | 2000-06-07 |
| JP4223068B2 (ja) | 2009-02-12 |
| US20030073080A1 (en) | 2003-04-17 |
| US6392028B1 (en) | 2002-05-21 |
| JP2008167755A (ja) | 2008-07-24 |
| IL131688A (en) | 2007-09-20 |
| US20020102540A1 (en) | 2002-08-01 |
| EP1005366A4 (en) | 2004-05-19 |
| AU6938698A (en) | 1998-09-22 |
| IL131688A0 (en) | 2001-03-19 |
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